The purpose of the proposed research is to elucidate the cellular mechanism of action of methaqualone abuse. Our earlier studies have indicated selective inhibition of nicotinamide adenine dinucleotide dependent oxidations by methaqualone without affecting nicotinamide adenine dinucleotide independent oxidation of sodium succinate by rat brain homogenate and isolated mitochondria. Various objectives of this proposal are to investigate in vivo effects of the administation of methaqualone in experimental animals and in vitro effects of methaqualine on isolated enzyme preparations obtained from normal and methaqualone treated animals to study methaqualone effects on: 1) microsomal drug metabolizing enzymes on biotransformation of drugs; 2) enzymes involved in the biosynthesis and metabolism of biologically active amines (epinephrine, norepinephrine, 3,4- dihydroxyphenylethylamine, 5- hydroxytrytamine) and their relation to tissue concentration and uptake in various subcellular cytoplasmic components and the urinary metabolites of these neurohumors or neurotransmitters; 3) adenyl cyclase and phosphodiesterase system together with the determination of urinary concentration of cyclic-AMP; 4) serum growth hormone levels measured by the use of radioimmunoassay techniques and 5) drug interactions (modification of the effects of other central nervous system active drugs) in animals treated with methaqualone for prolonged periods of up to six months to elucidate the cellular basis for the sensitivity of these drugs during methaqualone abuse. These investigations are focussed to develop therapeutic measures (introduction of new drugs with the knowledge of their cellular effects) to reduce methaqualone abuse and consequently to wipe out this social disease which is fast increasing in the modern society.